Method for preparing degradable drug-loaded microsphere for embolization, and product obtained therefrom

Abstract

A method for preparing a degradable drug-loaded microsphere for embolization and a product obtained therefrom, includes the steps of: dissolving a degradable material in an organic solvent, then adding a drug and mixing well to form a suspension or solution; then pouring the drug-containing suspension or solution into an aqueous solution of polyvinyl alcohol, stirring, and thereafter adding water twice for dilution, to prepare the degradable drug-loaded microsphere. The microsphere prepared by the present invention has the advantages of having a controllable particle size, a high drug loading capacity, and a regular spherical shape, being convenient for sieve sizing and accurate particle-size indication, and being accurately targeted to an embolized blood vessel, and the like, and thus has a good application prospect in interventional embolization therapy.

What is claimed is: 
     
       1. A method for preparing a degradable drug-loaded microsphere for embolization, comprising the steps of:
 (1) mixing a degradable material with an organic solvent to form a solution, adding a drug into the solution, and uniformly dispersing the drug to form a suspension or solution; 
 (2) adding the aforementioned suspension or solution into an aqueous PVA solution, stirring, and thereafter adding water twice into the aqueous PVA solution for dilution to obtain a microsphere, wherein each time after the water is added the mixture is stirred; and 
 (3) collecting, washing and drying the obtained microsphere to obtain the degradable drug-loaded microsphere for embolization, wherein in step (2), the volume of water added for the first time is 0.5-4 times larger than that of the aqueous PVA solution, and the volume of water added for the second time is 0.5-4 times larger than that of the aqueous PVA solution. 
 
     
     
       2. The method of  claim 1 , wherein the degradable material is one or more of poly(d,l-lactic-co-glycolic acid), poly(L-lactide-co-epsilon-caprolactone), polycaprolactone, methoxy poly(ethylene glycol)-poly(lactide), poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-co-glycolide), polydioxanone and poly(trimethylene carbonate). 
     
     
       3. The method of  claim 1 , wherein the drug is one or more of anti-tumor drugs. 
     
     
       4. The method of  claim 3 , wherein the drug is one or more of paclitaxel, rapamycin, 5-fluorouracil, cisplatin, doxorubicin, irinotecan, oxaliplatin, docetaxel, gemcitabine, pirarubicin, epirubicin, avastin, rituximab, and lenalidomide. 
     
     
       5. The method of  claim 3 , wherein the drug is one or more of rapamycin, 5-fluorouracil, cisplatin, doxorubicin, irinotecan, pirarubicin and epirubicin. 
     
     
       6. The method of  claim 1 , wherein the organic solvent is a mixture of dichloromethane and a poor solvent, and the poor solvent is one or more of acetone, ethyl acetate, ethanol, n-heptane, isohexane, ether and silicone oil. 
     
     
       7. The method of  claim 1 , wherein in step (1) the concentration of the degradable material in the organic solvent is 0.2-0.7 g/ml, and preferably the concentration of the degradable material in the organic solvent is 0.3-0.5 g/ml. 
     
     
       8. The method of  claim 1 , wherein in step (1) the mass ratio of the drug to the degradable material is 0.1-3:1, and preferably the mass ratio of the drug to the degradable material is 0.1-1:1. 
     
     
       9. The method of  claim 1 , wherein in step (1) the drug is uniformly dispersed by using ultrasound. 
     
     
       10. The method of  claim 1 , wherein in step (2) the concentration of the aqueous PVA solution is 1-45 wt %, and preferably the concentration of the aqueous PVA solution is 8-15 wt %. 
     
     
       11. The method of  claim 1 , wherein in step (2), the volume ratio of the aqueous PVA solution to the suspension or solution of step (1) is 1.5-50:1, and preferably the volume ratio of the aqueous PVA solution to the suspension or solution of step (1) is 1.5-10:1, and more preferably the volume ratio of the aqueous PVA solution to the suspension or solution of step (1) is 1.5-3:1. 
     
     
       12. The method of  claim 1 , wherein in step (2) the stirring speed is 100-400 rpm. 
     
     
       13. The method of  claim 1 , wherein in step (2), after the suspension or solution is added into the aqueous PVA solution, the mixture is stirred for 1-15 min, then diluted with water, stirred for 1-30 min, then diluted with water again, and stirred for 1-150 min. 
     
     
       14. The method of  claim 1 , wherein in step (2), after the suspension or solution is added into the aqueous PVA solution, the mixture is stirred for 1-15 min, then diluted with water, stirred for 1-20 min, then diluted with water again, and stirred for 1-30 min. 
     
     
       15. The method of  claim 1 , wherein the obtained microsphere has a particle size of 100-2000 μm. 
     
     
       16. A degradable drug-loaded microsphere for embolization prepared by the method for preparing the degradable drug-loaded microsphere for embolization of any of  claim 1 . 
     
     
       17. The degradable drug-loaded microsphere for embolization of  claim 16 , wherein the degradable drug-loaded microsphere for embolization has a degradation time of 20-60 days.